clinical trial comparing a biosimilar eptacog alfa with novoseven, in patients with hemophilia with inhibitors

Conditions: Hemophilia A or B With Inhibitor

Summary: the purpose of this multicentre, randomized, double-blinded, single dose, two-way cross-over study, is to compare the pharmacokinetics (pk) and pharmacodynamic (pd) of two different doses of the biosimilar eptacog alfa (activated) with novoseven in 48 patients, adult and children (\>12 years), not bleeding, with hemophilia a or b with inhibitors. patients will be randomized to receive either a single dose of eptacog alfa biosimilar 90 μg/kg or 270 μg/kg and one single dose of novoseven 90 μg/kg or 270 μg/kg, or vice versa, with doses separated by a washout period. all patients will be followed 12 months and will receive biosimilar eptacog alfa, on demand, for every bleeding episode that should occur - or - for prophylaxis, with the aim of monitoring of inhibiting antibody formation, lack of efficacy and collection of safety data.

forty-eight patients enrolled, not bleeding, will be randomized to receive two injections separated by a washout period of 3 days (t1/2 = 2.3h). patients are centrally registered and randomized to receive in a 2x2 cross-over setting either a single dose of two for the following products: a: aryoseven 90 µg/kg and b: novoseven 90 µg/kg - or - c: aryoseven 270 µg/kg and d: novoseven 270 µg/kg. patients will be hospitalized at the time of study medication administration and plasma sampling. before any treatment, a blood sample will be obtained in all patients for testing for immunogenicity.

Eligibility criteria:
inclusion criteria: * confirmed diagnosis of congenital hemophilia a or b with inhibitors to fviii or fix titer \>5 bethesda units (bu) * with \> 2 episodes of bleeding/year requiring treatment with fvii infusions, non in bleeding status * male subjects * adult and children (\>12 years) * written informed consent to the protocol to be eligible for the study. for minor patients, parent/legal guardian will provide consent and, when possible, patient assent will also be obtained. for compromised patients, their designated proxy must provide informed consent. * for the pk/pd phase, patients will be hospitalized at the time of study medication administration for plasma sampling (2 times during the study). exclusion criteria: * any other type of congenital or acquired coagulopathy, such as liver disease (hepatitis), vitamin k deficiency, uremia, malignancy. * antibodies against factor vii * ongoing bleeding prophylaxis regimens with novoseven or planned to occur during the trial * patients who have received routine (prophylactic) treatment with rfviia in the period between screening visit (visit 1) and visit 2 of this study (first dose administration) * platelet count less than 100.000 platelets/microliter (at screening visit) * any clinical sign or known history of an arterial thrombotic event or deep venous- thrombosis or pulmonary embolism * hiv positive with current cd4+ count of less than 200/µl * liver cirrhosis * factor viii/ix immune tolerance induction regimen planned to occur during the trial * known hypersensitivity to the study medication * parallel participation in another experimental drug trial. * parallel participation in another marketed drug trial that may affect the primary endpoint of the study